Novel biomarkers and endoscopic techniques for diagnosing pancreaticobiliary malignancy

The UK incidence of pancreatic ductal adenocarcinoma is 9 per 100,000 population, and biliary tract cancer occurs at a rate of 1-2 per 100,000. The incidence of both cancers is increasing annually and these tumours continue to be diagnosed late and at an advanced stage, limiting options for curative treatment. Population-based screening programmes do not exist for these cancers, and diagnosis currently is dependent on symptom recognition, but often symptoms are not present until the disease is advanced. Recently, a number of promising blood and urine biomarkers have been described for pancreaticobiliary malignancy and are summarised in this review. Novel endoscopic techniques such as single-operator cholangioscopy and confocal endomicroscopy have been used in some centres to enhance standard endoscopic diagnostic techniques and are also evaluated in this review

Controversies in the management of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) remains a rare but significant disease, which affects mainly young males in association with inflammatory bowel disease. There have been few advances in the understanding of the pathogenesis of the condition and no therapeutics with proven mortality benefit aside from liver transplantation. There remain areas of controversy in the management of PSC which include the differentiation from other cholangiopathies, in particular immunoglobulin G4 related sclerosing cholangitis, the management of dominant biliary strictures, and the role of ursodeoxycholic acid. In addition, the timing of liver transplantation in PSC remains difficult to predict with standard liver severity scores. In this review, we address these controversies and highlight the latest evidence base in the management of PSC

Anticonvulsant Activity of Carissa carandas Linn. Root Extract in Experimental Mice

Purpose: The aim of the present study was to investigate anticonvulsant effect of the ethanolic extract of the roots of Carissa carandas (ERCC) on electrically and chemically induced seizures.Methods: The ethanolic extract of the roots of C. carandas (100, 200 and 400 mg/kg, i.p.) was studied for its anticonvulsant effect on maximal electroshock-induced seizures and pentylenetetrazole-, picrotoxin-, bicuculline- and N-methyl-dl-aspartic acid-induced seizures inmice. The latency of tonic convulsions and the number of animals protected from tonic convulsions were noted.Results: ERCC (100-400 mg/kg) significantly reduced the duration of seizures induced by maximal electroshock (MES). However, only 200 and 400mg/kg of the extract conferred protection (25 and 50%, respectively) on the mice. The same doses also protected animals from pentylenetetrazole-induced tonic seizures and significantly delayed the onset of tonic seizures produced by picrotoxin and N-methyl-dl-aspartic acid. The extract had no effect on bicuculline-induced seizures.Conclusion: The data suggest that the ethanolic root extract of C. carandas may produce its anticonvulsant effects via non-specific mechanisms since it reduced the duration of seizures produced by maximal electroshock as well as delayed the latency of seizures produced by pentylenetetrazole and picrotoxin

An effective method for extraction and polymerase chain reaction (PCR) amplification of DNA from formalin preserved tissue samples of snow leopard

Formalin-preserved biological samples obtained from endangered species are valuable in assessing genetic diversity. To make use of snow leopard samples preserved in formalin over a period of two to seven years, we optimized the method of extracting DNA from these samples. We used (a) phenol chloroform : isoamyl alcohol, (b) the Qiagen DNeasy Blood and Tissue Kit (Qiagen, Germany), (c) the Qiagen DNeasy Blood and Tissue Kit after treating the samples with NaOH for three days and (d) the Qiagen DNeasy Blood and Tissue Kit after treating the samples with phosphate buffered saline (PBS) for three days. The usefulness of the extracted DNA was assessed on the basis of mitochondrial (150 to 550 bp) and nuclear (95 to 229 bp) markers. There was no PCR amplification with the first two methods. The PCR amplification with the NaOH and PBS treatment had a success rate of 30 to 100% for both mitochondrial and nuclear markers. The PBS method is the best method for extraction of DNA from formalin-preserved samples of longer period (two to seven years) because of higher success rate in amplifying mitochondrial gene of ca. 550 bp (60%) than the NaOH method (28%). The overall amplification of microsatellite markers in such samples was also higher in samples treated with PBS (43 to 100%) than NaOH (0 to 100%). The PCR products obtained were confirmed through DNA sequencing to be of snow leopard origin. The optimized protocol will enable genetic studies to be conducted on tissue samples of other species that have been preserved in formalin. The protocol will be particularly useful for species that are elusive and from which it is difficult to collect fresh tissue samples.Keywords: Formalin, polymerase chain reaction (PCR), mtDNA, microsatellites, snow leopardAfrican Journal of Biotechnology Vol. 12(22), pp. 3399-340

A study of greater sciatic notch as an indicator of sex determination of adult human hip bone

Background: Sex determination from bone is very useful for anatomy, forensic and anthropology personnel. Hip bone is most commonly used bone for sex identification. Aims: Present study was carried out to assess the efficacy of greater sciatic notch to determine sex. Material & Methods: Study sample consisted of 108 adult human hip bones (27 male and female, each of both side) obtained from Anatomy department, P.D.U. Medical College, Rajkot, Gujarat. Present study focused on two indices of greater sciatic notch. Index1 = (maximum breadth of greater sciatic notch/maximum depth of greater sciatic notch)*100 and Index2= (length of posterior segment of maximum breadth of greater sciatic notch /maximum breadth of greater sciatic notch)*100. Results: Index 1 identified correct sex in 51.85% of right male, 44.44% of right female, 44.44% of left male and 48.14% of left female bones. While index 2 identified correct sex in 70.37% of right male , 66.66% of right female, 55.55% of left male and 59.25% of left female bones. Conclusion: This study indicates that these indices are helpful for sex determination in both sexes with index 2 being more sensitive as compared to index 1

Accuracy of physical examination in the diagnosis of hypothyroidism: a cross-sectional, double-blind study

Background: Hypothyroidism is a common, potentially treatable endocrine disorder. Since hypothyroidism is not always associated with the signs and symptoms typically attributed to it, the diagnosis is often missed. Conversely, patients with typical signs and symptoms may not have the disease when laboratory tests are performed. Aims: We aimed to determine the accuracy of physical examination in the diagnosis of hypothyroidism. Setting and design: Prospective, hospital-based, cross-sectional diagnostic study. Material and Methods: Consecutive outpatients from the medicine department were screened and an independent comparison of physical signs (coarse skin, puffy face, slow movements, bradycardia, pretibial oedema and ankle reflex) against thyroid hormone assay (TSH and FT4) was performed. Statistical analysis: Diagnostic accuracy was measured as sensitivity, specificity, positive likelihood ratios, negative likelihood ratios and positive and negative predictive values. Results: Of the 1450 patients screened, 130 patients (102 women and 28 men) underwent both clinical examination and thyroid function tests. Twenty-three patients (18%) were diagnosed to have hypothyroidism by thyroid hormone assays. No single sign could easily discriminate a euthyroid from a hypothyroid patient (range of positive likelihood ratio (LR+) 1.0 to 3.88; range of negative likelihood ratio (LR-): 0.42 to 1.0). No physical sign generated a likelihood ratio large enough to increase the post-test probability significantly. The combination of signs that had the highest likelihood ratios (coarse skin, bradycardia and delayed ankle reflex) was associated with modest accuracy (LR+ 3.75; LR- 0.48). Conclusion: Clinicians cannot rely exclusively on physical examination to confirm or rule out hypothyroidism. Patients with suspected hypothyroidism require a diagnostic workup that includes thyroid hormone assays

Hepatolithiasis with biliary ascariasis – a case report

BACKGROUND: Biliary ascariasis is regarded as possible etiological factor for hepatolithiasis. Here we report one case of a patient with hepatolithiasis with biliary ascariasis who developed a liver abscess, which was treated with partial hepatectomy. CASE PRESENTATION: A young adult female presented with epigastric pain and vomiting with repeated attacks of cholangitis. ERCP showed evidence of multiple intrahepatic calculi with the development of abscess in the left lobe of liver. The patient underwent partial hepatectomy and was found to have biliary ascariasis on histology. She was treated with antihelmenthic therapy and has had an uneventful postoperative period of 2 years. CONCLUSION: Biliary ascariasis with hepatolithiasis, although rare, should be considered in endemic countries

Molecular Valves for Controlling Gas Phase Transport Made from Discrete Angstrom-Sized Pores in Graphene

An ability to precisely regulate the quantity and location of molecular flux is of value in applications such as nanoscale 3D printing, catalysis, and sensor design. Barrier materials containing pores with molecular dimensions have previously been used to manipulate molecular compositions in the gas phase, but have so far been unable to offer controlled gas transport through individual pores. Here, we show that gas flux through discrete angstrom-sized pores in monolayer graphene can be detected and then controlled using nanometer-sized gold clusters, which are formed on the surface of the graphene and can migrate and partially block a pore. In samples without gold clusters, we observe stochastic switching of the magnitude of the gas permeance, which we attribute to molecular rearrangements of the pore. Our molecular valves could be used, for example, to develop unique approaches to molecular synthesis that are based on the controllable switching of a molecular gas flux, reminiscent of ion channels in biological cell membranes and solid state nanopores.Comment: to appear in Nature Nanotechnolog

Personal Drug Selection: Problem-Based Learning in Pharmacology: Experience from a Medical School in Nepal

BACKGROUND: At the Manipal College of Medical Sciences, Pokhara, Nepal, Pharmacology is taught during the first four semesters of the undergraduate medical course. Personal or P-drug selection is an important exercise. The present study was carried out to obtain student opinion about the P-drug learning sessions, the assessment examinations, and on the small group dynamics. METHOD: The practical sessions on P-drug selection are carried out in small groups. Student feedback about the session was obtained using focus group discussions. The focus groups were selected to represent both genders and the three main nationalities, Nepalese, Indians, and Sri Lankans. There were four Nepalese, five Indians, and three Sri Lankans. Within each nationality and gender category the students were randomly selected. The respondents were explained the objectives of the study and were invited to participate. Written informed consent was obtained. The discussion lasted around two hours and was conducted in the afternoon in two groups of six students each. The first author (PRS) acted as a facilitator. The responses were recorded and analyzed qualitatively. RESULTS: The overall student opinion was positive. Around 25% (3 respondents) of respondents were confused about whether P-drugs were for a disease or a patient. Group consensus was commonly used to give numerical values for the different criteria. The large number of brands created problems in calculating cost. The students wanted more time for the exercise in the examination. Formative assessment during the learning sessions may be considered. The group members usually got along well. Absenteeism was a problem and not all members put in their full effort. The physical working environment should be improved. CONCLUSIONS: Based on what the students say, the sessions on P-drugs should be continued and strengthened. Modifications in the sessions are required. Sessions during the clinical years and internship training can be considered